Early Infliximab Trough Levels Predict the Long-term Efficacy of Infliximab in a Randomized Controlled Trial in Patients with Active Crohn’s Disease Comparing, between CT-P13 and Originator Infliximab
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn’s disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.
Abstract
Background/Aims: The clinical efficacy and safety of CT-P13 are comparable to originator infliximab for Crohn’s disease in CT-P13 3.4 study (NCT02096861). We performed a multivariate logistic analysis to demonstrate the association between early infliximab trough levels and treatment outcomes of CT-P13 and originator infliximab. Methods: Early serum infliximab trough levels and anti-drug antibody (ADA) levels were compared between CT-P13 (n=100) and originator infliximab (n=98) groups. Receiver operating characteristic (ROC) analysis and multivariate logistic analysis were conducted to identify optimal cutoffs of serum infliximab trough levels and predictive factors for clinical outcomes. Results: The median infliximab trough levels were not different between CT-P13 and originator infliximab groups at week 6, week 14, and in median ADA levels at week 14, respectively. ROC analysis found an infliximab concentration threshold of 4.5 μg/mL at week 6 and 4.0 μg/mL at week 14 as the cutoff value with the highest accuracy for the prediction of clinical outcomes. Serum infliximab trough levels at weeks 6 and 14 predicted clinical remission at weeks 30 and 54, and endoscopic remission at week 54. The combinations of clinical remission or C-reactive protein normalization with an early infliximab trough level improved the prediction of long-term clinical or endoscopic remission. Conclusions: A threshold in serum infliximab trough level at week 6 and week 14 was highly predictive for long-term clinical outcomes. There were no statistical differences in serum infliximab trough levels and ADA levels between CT-P13 and originator infliximab.
참고문헌 (32)
- Hanauer SB, "Maintenance infliximab for Crohn’s disease : the ACCENT I randomised trial", Lancet, 359, pp.1541~1549 (2002)
- Sands BE, "Infliximab maintenance therapy for fistulizing Crohn’s disease", N Engl J Med, 350, pp.876~885 (2004)
- Ye BD, "Efficacy and safety of biosimilar CT-P13 compared with originator infliximab in patients with active Crohn’s disease : an international, randomised, double-blind, phase 3 non-inferiority study", Lancet, 393, pp.1699~1707 (2019)
- Jørgensen KK, "Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab(NORSWITCH) : a 52-week, randomised, double-blind, noninferiority trial", Lancet, 389, pp.2304~2316 (2017)
- Argollo M, "Optimizing biologic therapy in IBD : how essential is therapeutic drug monitoring?", Nat Rev Gastroenterol Hepatol, 17, pp.702~710 (2020)
- Paul S, "Therapeutic drug monitoring of infliximab and mucosal healing in inflammatory bowel disease : a prospective study", Inflamm Bowel Dis, 19, pp.2568~2576 (2013)
- Papamichael K, "Association between serum infliximab trough concentrations during maintenance therapy and biochemical, endoscopic, and histologic remission in Crohn’s disease", Inflamm Bowel Dis, 24, pp.2266~2271 (2018)
- Feuerstein JD, "American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease", Gastroenterology, 153, pp.827~834 (2017)
- Lamb CA, "British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults", Gut, 68(Suppl 3), pp.s1~s106 (2019)
- Papamichael K, "Appropriate therapeutic drug monitoring of biologic agents for patients with inflammatory bowel diseases", Clin Gastroenterol Hepatol, 17, pp.1655~1668 (2019)
- Eron Fabio Miranda, "Correlation of serum levels of anti-tumor necrosis factor agents with perianal fistula healing in Crohn’s disease: a narrative review", Intestinal research, 19(3), pp.255~264 (2021), 대한장연구학회[DOI]
- Ben-Horin S, "Cross-immunogenicity : antibodies to infliximab in Remicade-treated patients with IBD similarly recognise the biosimilar Remsima", Gut, 65, pp.1132~1138 (2016)
- Fiorino G, "Full interchangeability in regard to immunogenicity between the infliximab reference biologic and biosimilars CT-P13 and SB2 in inflammatory bowel disease", Inflamm Bowel Dis, 24, pp.601~606 (2018)
- Gecse KB, "Efficacy and safety of the biosimilar infliximab CT-P13 treatment in inflammatory bowel diseases : a prospective, multicentre, nationwide cohort", J Crohns Colitis, 10, pp.133~140 (2016)
- Gonczi L, "Prediction of shortand medium-term efficacy of biosimilar infliximab therapy. do trough levels and antidrug antibody levels or clinical and biochemical markers play the more important role?", J Crohns Colitis, 11, pp.697~705 (2017)
- Farkas K, "Efficacy of infliximab biosimilar CT-P13 induction therapy on mucosal healing in ulcerative colitis", J Crohns Colitis, 10, pp.1273~1278 (2016)
- Strik AS, "Serum concentrations after switching from originator infliximab to the biosimilar CT-P13 in patients with quiescent inflammatory bowel disease(SECURE) : an open-label, multicentre, phase 4 non-inferiority trial", Lancet Gastroenterol Hepatol, 3, pp.404~412 (2018)
- Martínez-Feito A, "Infliximab concentrations in two non-switching cohorts of patients with inflammatory bowel disease : originator vs. biosimilar", Sci Rep, 10, pp.17099~ (2020)
- Vuitton L, "IOIBD technical review on endoscopic indices for Crohn’s disease clinical trials", Gut, 65, pp.1447~1455 (2016)
- Bortlik M, "Infliximab trough levels may predict sustained response to infliximab in patients with Crohn’s disease", J Crohns Colitis, 7, pp.736~743 (2013)
- Singh N, "Early infliximab trough levels are associated with persistent remission in pediatric patients with inflammatory bowel disease", Inflamm Bowel Dis, 20, pp.1708~1713 (2014)
- Cornillie F, "Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab : a retrospective analysis of the ACCENT I trial", Gut, 63, pp.1721~1727 (2014)
- Sang Hyoung Park, "Biosimilars: concept, current status, and future perspectives in inflammatory bowel diseases", Intestinal research, 18(1), pp.34~44 (2020), 대한장연구학회
- Schulze K, "CT-P13(Inflectra™, Remsima™)monitoring in patients with inflammatory bowel disease", Biologicals, 44, pp.463~466 (2016)
- Reinisch W, "C-reactive protein, an indicator for maintained response or remission to infliximab in patients with Crohn’s disease : a post-hoc analysis from ACCENT I", Aliment Pharmacol Ther, 35, pp.568~576 (2012)
- Schnitzler F, "Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease : results from a single-centre cohort", Gut, 58, pp.492~500 (2009)
- Turner D, "STRIDE-II : an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease(STRIDE)Initiative of the International Organization for the Study of IBD(IOIBD) : determining therapeutic goals for treat-to-target strategies in IBD", Gastroenterology, 160, pp.1570~1583 (2021)
- Bar-Yoseph H, "Early drug and anti-infliximab antibody levels for prediction of primary nonresponse to infliximab therapy", Aliment Pharmacol Ther, 47, pp.212~218 (2018)
- Colombel JF, "Therapeutic drug monitoring of biologics for inflammatory bowel disease", Inflamm Bowel Dis, 18, pp.349~358 (2012)
- Maser EA, "Association of trough serum infliximab to clinical outcome after scheduled maintenance treatment for Crohn’s disease", Clin Gastroenterol Hepatol, 4, pp.1248~1254 (2006)
- Baert F, "Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease", N Engl J Med, 348, pp.601~608 (2003)
- Colombel JF, "Infliximab, azathioprine, or combination therapy for Crohn’s disease", N Engl J Med, 362, pp.1383~1395 (2010)